A patient takes aspirin 75 mg daily for secondary prevention of myocardial infarction. Why is such a low dose sufficient for antiplatelet effect when much higher doses are needed for analgesic and anti-inflammatory effects?

• A Low-dose aspirin irreversibly acetylates COX-1 in anucleate platelets; since platelets cannot synthesise new COX-1, TXA2 production is abolished for the platelet lifespan ✓
• B Low-dose aspirin selectively inhibits COX-2 in endothelial cells, increasing prostacyclin production
• C Low-dose aspirin reduces ADP release from platelet dense granules
• D Low-dose aspirin blocks the glycoprotein IIb/IIIa receptor on platelets

Explanation

Aspirin irreversibly acetylates the active-site serine of COX-1 (and COX-2). Platelets are anucleate and cannot synthesise new COX-1, so a single dose abolishes TXA2 production for the platelet's entire 7-10 day lifespan. Low doses sufficiently acetylate platelet COX-1 in the portal circulation before systemic distribution, providing sustained antiplatelet effect. Higher doses are needed for anti-inflammatory effects because nucleated cells (including inflammatory cells) can synthesise new COX-2 continuously, and reversible competitive inhibition at inflammatory sites requires sustained higher concentrations.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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